OBJECTIVES: To further define the mechanism(s) controlling renin secretion. Experimental observations suggest that renin secretion is controlled in part by renal perfusion pressure (RPP), in part by some aspect of NaCl transport in the macula densa segment of the nephron, and in part by activity of the renal nerves and the plasma concentrations of various organic and inorganic substances. METHODS: Because it is difficult to control, in vivo, the many variables that affect secretion, rat renal cortical slices and isolated-perfused rat kidneys will be used in these investigation. Current work with slices suggests that secretion is directly related to transmembrane Na gradient (across either the macula densa or the juxtaglomerular cells; both are present in this preparation). The effects on secretion of increasing intracellular Na (inhibition of Na,K-ATPase activity) or by decreasing extracellular Na will be investigated further; interactions of ouabain with extracellular K will be investigated as well. The calcium-dependency of the responses will be assessed by using pharmacologic Ca-antagonists (D-600) and Ca-chelator (EGTA). The mechanism of inhibition of secretion by angiotensin II and by antidiuretic hormone will be investigated using sodium and calcium "channel blockers". The calcium-dependency of the baroreceptor mechanism of control of secretion will be investigated by measuring secretion as a function of RPP, before and after D-600 treatment of the isolated-perfused rat kidney. SIGNIFICANCE: In view of the physiologic/pathophysiologic roles played by the renin-angiotensin-aldosterone axis in salt and water balance and in regulation of arterial blood pressure, understanding the control of renin secretion is of great importance.